Lanfredini, Simone, Olivero, Carlotta ORCID: 0000-0002-8961-6703, Borgogna, Cinzia, Calati, Federica, Powell, Kathryn, Davies, Kelli-Jo, De Andrea, Marco ORCID: 0000-0002-3188-5783, Harries, Sarah, Tang, Hiu Kwan Carolyn, Pfister, Herbert, Gariglio, Marisa and Patel, Girish K. (2017). HPV8 Field Cancerization in a Transgenic Mouse Model Is due to Lrig1+Keratinocyte Stem Cell Expansion. J. Invest. Dermatol., 137 (10). S. 2208 - 2217. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1747

Full text not available from this repository.

Abstract

beta-Human papillomaviruses (HPVs) cause near ubiquitous latent skin infection within long-lived hair follicle (HF) keratinocyte stem cells. In patients with epidermodysplasia verruciformis, beta-HPV viral replication is associated with skin keratosis and cutaneous squamous cell carcinoma. To determine the role of HF keratinocyte stem cells in beta-HPV-induced skin carcinogenesis, we utilized a transgenic mouse model in which the keratin 14 promoter drives expression of the entire HPV8 early region (HPV8tg). HPV8tg mice developed thicker skin in comparison with wild-type littermates consistent with a hyperproliferative epidermis. HF keratinocyte proliferation was evident within the Lrig1 + keratinocyte stem cell population (69 vs. 55%, P < 0.01, n = 7), and not in the CD34+, LGR5+, and LGR6+ keratinocyte stem cell populations. This was associated with a 2.8-fold expansion in Lrig1+ keratinocytes and 3.8-fold increased colony-forming efficiency. Consistent with this, we observed nuclear p63 expression throughout this population and the HF infundibulum and adjoining inter-follicular epidermis, associated with a switch from p63 transcriptional activation isoforms to Delta Np63 isoforms in HPV8tg skin. Epidermodysplasia verruciformis keratosis and in some cases actinic keratoses demonstrated similar histology associated with b-HPV reactivation and nuclear p63 expression within the HF infundibulum and perifollicular epidermis. These findings would suggest that b-HPV field cancerization arises from the HF junctional zone and predispose to squamous cell carcinoma.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Lanfredini, SimoneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olivero, CarlottaUNSPECIFIEDorcid.org/0000-0002-8961-6703UNSPECIFIED
Borgogna, CinziaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Calati, FedericaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Powell, KathrynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Davies, Kelli-JoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
De Andrea, MarcoUNSPECIFIEDorcid.org/0000-0002-3188-5783UNSPECIFIED
Harries, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tang, Hiu Kwan CarolynUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfister, HerbertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gariglio, MarisaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patel, Girish K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-216768
DOI: 10.1016/j.jid.2017.04.039
Journal or Publication Title: J. Invest. Dermatol.
Volume: 137
Number: 10
Page Range: S. 2208 - 2217
Date: 2017
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1523-1747
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
BETA-PAPILLOMAVIRUS INFECTION; SKIN TUMORS; P63; EXPRESSION; PROLIFERATION; PROTEIN; DNA; IMMUNODEFICIENCY; KERATINOCYTES; SUPPRESSORMultiple languages
DermatologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/21676

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item